5-191755-G-A

Position:

• chr5-191755-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080478.3(LRRC14B):​c.217G>A​(p.Asp73Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,400,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: LRRC14B NM_001080478.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.30

Genes affected

LRRC14B (HGNC:37268): (leucine rich repeat containing 14B) The protein encoded by this gene is a leucine-rich repeat containing protein that is a member of the PRAME family. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39170444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC14B	NM_001080478.3	c.217G>A	p.Asp73Asn	missense_variant	1/2	ENST00000328278.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC14B	ENST00000328278.4	c.217G>A	p.Asp73Asn	missense_variant	1/2	1	NM_001080478.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400358 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 691600

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000125

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2023

The c.217G>A (p.D73N) alteration is located in exon 1 (coding exon 1) of the LRRC14B gene. This alteration results from a G to A substitution at nucleotide position 217, causing the aspartic acid (D) at amino acid position 73 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.24
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.25		Gain of loop (P = 0.0851);
MVP		0.32
MPC		0.75
ClinPred		0.77	D
GERP RS		5.2
Varity_R		0.12
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs749692583; hg19: chr5-191870; COSMIC: COSV52045148; COSMIC: COSV52045148;